@article{2ffcd768cd3d4117bceffb9dfb832328,
title = "Predictors and outcomes of heart failure with mid-range ejection fraction",
abstract = "AIMS: While heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) are well described, determinants and outcomes of heart failure with mid-range ejection fraction (HFmrEF) remain unclear. We sought to examine clinical and biochemical predictors of incident HFmrEF in the community.METHODS AND RESULTS: We pooled data from four community-based longitudinal cohorts, with ascertainment of new heart failure (HF) classified into HFmrEF [ejection fraction (EF) 41-49%], HFpEF (EF ≥50%), and HFrEF (EF ≤40%). Predictors of incident HF subtypes were assessed using multivariable Cox models. Among 28 820 participants free of HF followed for a median of 12 years, there were 200 new HFmrEF cases, compared with 811 HFpEF and 1048 HFrEF. Clinical predictors of HFmrEF included age, male sex, systolic blood pressure, diabetes mellitus, and prior myocardial infarction (multivariable adjusted P ≤ 0.003 for all). Biomarkers that predicted HFmrEF included natriuretic peptides, cystatin-C, and high-sensitivity troponin (P ≤ 0.0004 for all). Natriuretic peptides were stronger predictors of HFrEF [hazard ratio (HR) 2.00 per 1 standard deviation increase, 95% confidence interval (CI) 1.81-2.20] than of HFmrEF (HR 1.51, 95% CI 1.20-1.90, P = 0.01 for difference), and did not differ in their association with incident HFmrEF and HFpEF (HR 1.56, 95% CI 1.41-1.73, P = 0.68 for difference). All-cause mortality following the onset of HFmrEF was worse than that of HFpEF (50 vs. 39 events per 1000 person-years, P = 0.02), but comparable to that of HFrEF (46 events per 1000 person-years, P = 0.78).CONCLUSIONS: We found overlap in predictors of incident HFmrEF with other HF subtypes. In contrast, mortality risk after HFmrEF was worse than HFpEF, and similar to HFrEF.",
keywords = "Aged, Cause of Death/trends, Echocardiography, Female, Follow-Up Studies, Heart Failure/diagnosis, Heart Ventricles/diagnostic imaging, Humans, Incidence, Male, Middle Aged, Prognosis, Prospective Studies, Risk Assessment, Stroke Volume/physiology, Survival Rate/trends, United States/epidemiology",
author = "Vijeta Bhambhani and Kizer, {Jorge R} and Lima, {Joao A C} and {van der Harst}, Pim and Hossein Bahrami and Matthew Nayor and {de Filippi}, {Christopher R} and Danielle Enserro and Blaha, {Michael J} and Mary Cushman and Wang, {Thomas J} and Gansevoort, {Ron T} and Fox, {Caroline S} and Gaggin, {Hanna K} and Kop, {Willem J} and Kiang Liu and Vasan, {Ramachandran S} and Psaty, {Bruce M} and Lee, {Douglas S} and Brouwers, {Frank P} and Hillege, {Hans L} and Bartz, {Traci M} and Benjamin, {Emelia J} and Cheeling Chan and Matthew Allison and Gardin, {Julius M} and Januzzi, {James L} and Daniel Levy and Herrington, {David M} and {van Gilst}, {Wiek H} and Bertoni, {Alain G} and Larson, {Martin G} and {de Boer}, {Rudolf A} and Gottdiener, {John S} and Shah, {Sanjiv J} and Ho, {Jennifer E}",
note = "Funding Information: This work was partially supported by the National Heart, Lung, and Blood Institute (NHLBI), including the Framingham Heart Study (contract N01-HC25195 and HHSN268201500001I), the Cardiovascular Health Study (HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grants U01HL080295 and U01HL130114 from the NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. MESA and the MESA SHARe project are conducted and supported by the NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. Funding support for the MESA Renal Function dataset was provided by grant DK083538-01. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi .org. The PREVEND study has been made possible by grants from the Dutch Kidney Foundation. R.A.d.B. is supported by the Netherlands Heart Foundation (CVON-DOSIS, grant 2014-40) and the Innovational Research Incentives Scheme programme of the Netherlands Organization for Scientific Research (NWO VIDI, grant 917.13.350). M.N. received support from the Clinical Skills Development Core Training Grant U10HL110337 from the NHLBI. J.E.H. is supported by K23-HL116780 and a Hassenfeld Research Scholar Award (Massachusetts General Hospital, Boston, MA). D.S.L. is supported by a mid-career award from the Heart and Stroke Foundation of Canada, and is the Ted Rogers Chair in Heart Function Outcomes. In FHS samples, measurement of soluble ST2 was performed by Critical Diagnostics, Inc., and measurement of high-sensitivity troponin I was performed by Singulex, Inc. J.E.H. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conflict of interests: J.R.K. reports stock ownership from Gilead Sciences, Inc., Pfizer, Inc. and Amgen. M.N. reports grants from NHLBI. C.R.dF. reports grants and personal fees from Roche Diagnostics; personal fees from Radiometer, Alere, Siemens, Ortho Diagnostics, Metanomics, Quintiles, UpToDate, Medscape, and grants from Abbott Diagnostics. M.J.B. reports grants and personal fees from FDA and Amgen/Amgen Foundation; grants from NIH/NHLBI, AHA and Aetna Foundation; personal fees from ACC, Novartis, MedImmune, Sanofi/Regeneron, and Akcea. C.S.F. is currently an employee of Merck. H.K.G. reports grants and personal fees from Roche Diagnostics; grants from Portola; personal fees from Amgen, Ortho clinical; clinical endpoint committee for Echo-Sense and Radiometer. T.M.B. reports grants from NIH. E.J.B. reports grants from NIH/NHLBI, Assoc. Editor for AHA/NIH and CARDIA OSMB from NIH/NCBI. J.L.J. reports grants and personal fees from Roche, Siemens; grants from Prevencio and Singulex; personal fees from Abbott, Philips and Ortho Clinical. A.G.B. reports grants from NIH/NHLBI. R.A.dB. reports grants from AstraZeneca, Bristol Meyers Squibb, Trevena, Roche, and Novartis. J.E.H. reports grants from National Institutes of Health and Massachusetts General Hospital. The other authors have no conflicts to disclose. Funding Information: This work was partially supported by the National Heart, Lung, and Blood Institute (NHLBI), including the Framingham Heart Study (contract N01-HC25195 and HHSN268201500001I), the Cardiovascular Health Study (HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grants U01HL080295 and U01HL130114 from the NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. MESA and the MESA SHARe project are conducted and supported by the NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. Funding support for the MESA Renal Function dataset was provided by grant DK083538-01. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. The PREVEND study has been made possible by grants from the Dutch Kidney Foundation. R.A.d.B. is supported by the Netherlands Heart Foundation (CVON-DOSIS, grant 2014-40) and the Innovational Research Incentives Scheme programme of the Netherlands Organization for Scientific Research (NWO VIDI, grant 917.13.350). M.N. received support from the Clinical Skills Development Core Training Grant U10HL110337 from the NHLBI. J.E.H. is supported by K23-HL116780 and a Hassenfeld Research Scholar Award (Massachusetts General Hospital, Boston, MA). D.S.L. is supported by a mid-career award from the Heart and Stroke Foundation of Canada, and is the Ted Rogers Chair in Heart Function Outcomes. In FHS samples, measurement of soluble ST2 was performed by Critical Diagnostics, Inc., and measurement of high-sensitivity troponin I was performed by Singulex, Inc. J.E.H. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Publisher Copyright: {\textcopyright} 2017 The Authors. European Journal of Heart Failure {\textcopyright} 2017 European Society of Cardiology",
year = "2018",
month = apr,
doi = "10.1002/ejhf.1091",
language = "English",
volume = "20",
pages = "651--659",
journal = "European Journal of Heart Failure",
issn = "1388-9842",
publisher = "Oxford University Press",
number = "4",
}